An Open-Labeled, Phase I Study to Evaluate the Safety and Tolerability of Apatinib With Nivolumab in Patients With Unresectable or Metastatic Cancer
Overview
- Phase
- Phase 1
- Intervention
- Apatinib
- Conditions
- Cancer
- Sponsor
- Elevar Therapeutics
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Number of Participants with Treatment Emergent Adverse Events (TEAEs)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This is an open-labeled, single-center, Phase I study to evaluate the safety, tolerability, and efficacy of apatinib with nivolumab treatment in participants with unresectable or metastatic cancer. Total study duration will be approximately 50 months: 12 months of recruitment plus 6 months of treatment and subsequent survival follow up.
Detailed Description
Primary objectives: * To evaluate the safety and tolerability of apatinib with nivolumab in participants with unresectable or metastatic cancer. * To assess efficacy by objective response rate (ORR), best overall response (BOR), time to response (TTR), and duration of response (DoR) per response evaluation criteria for solid tumors (RECIST) v1.1 and/or response evaluation criteria for solid tumors for immune-based therapeutics (iRECIST). * To assess disease control rate (DCR), and duration of disease control (DDC) by RECIST v1.1, and/or iRECIST. Secondary objectives: * To evaluate the efficacy of apatinib with nivolumab in participants with unresectable or metastatic cancer as measured by: * Overall survival (OS) * Progression-free survival (PFS) * Event-free survival (EFS)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Documented primary diagnosis of histologic- or cytologic-confirmed solid tumor cancer inclusive of gastric adenocarcinoma, renal cell carcinoma, melanoma, non-small cell lung cancer (NSCLC), breast cancer, angiosarcoma, leiomyosarcoma, synovial sarcoma, and alveolar soft part sarcoma or other solid tumor for which anti-Vascular endothelial growth factor receptor (VEGFR)2 targeted therapy could be applicable.
- •Locally advanced unresectable or metastatic disease.
- •Nivolumab treatment naive and able to begin nivolumab treatment concurrently with initiation of apatinib or have received at least 3 doses of nivolumab treatment and are continuing nivolumab therapy.
- •1 or more measurable lesions per RECIST v1.
- •Participants who have adequate bone-marrow, renal and liver function including:
- •Hematologic: absolute neutrophil count ≥ 1,500/ cubic millimetre (mm\^3), platelets≥ 100,000/mm\^3, hemoglobin ≥ 9.0 grams (g)/ per decilitre (dL) (blood transfusion to meet the inclusion criteria within 2 weeks is not allowed).
- •Renal: serum creatinine \< 1.5× upper limit of normal (ULN); urinary protein should be\< 2+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria ≥ 2+, then a 24-hour urine or urine protein/creatinine ratio must be collected and must demonstrate \<2 g of protein in 24 hours to allow participation in the study.
- •Hepatic: serum bilirubin \< 1.5× ULN, aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0× ULN(≤ 4.0× ULN, if with liver metastases).
- •Blood coagulation tests: Partial thromboplastin time (PTT) and international normalized ratio (INR) ≤ 1.5× ULN and ≤ 1.5×ULN, respectively.
- •Eastern Cooperative Oncology Group (ECOG) performance status are evaluated to be ≤ 1 (Participants with ECOG performance status of 2 may be enrolled only with advance review and written approval by the medical monitor).
Exclusion Criteria
- •History of another malignancy within 2 years prior to enrollment, unless it does not pose a significant risk to life expectancy as per the investigator.
- •Central nervous system (CNS) metastases as shown by radiology records or clinical evidence of symptomatic CNS involvement in the last 3 months prior to enrollment. Participants are eligible if metastases have been treated and have returned to neurologic baseline or are neurologically stable (except for residual signs or symptoms related to the CNS treatment).
- •Cytotoxic chemotherapy, surgery, radiotherapy or other targeted therapies and checkpoint inhibitors (excluding nivolumab if not nivolumab treatment naive) within 3 weeks (4 weeks in cases of ramucirumab, mitomycin C, nitrosourea, lomustine; 1 week in case of biopsy) prior to enrollment (adjuvant radiotherapy given to local area for non-curative symptom relief is allowed until 2 weeks before enrollment).
- •Any other therapies including biological and approved therapies within 3 half-lives or 3 weeks whichever is longer and have not recovered from all toxicities from the treatment.
- •Therapy with clinically significant systemic anticoagulant or anti thrombotic agents within 7 days prior to enrollment that may prevent blood clotting and, in the investigator's opinion, could place the participants at risk. Maximum dose of 325 milligram (mg)/day of aspirin is allowed.
- •History of bleeding diathesis or clinically significant bleeding within 14 days prior to enrollment.
- •History of clinically significant thrombosis (bleeding or clotting disorder) within the past 3 months prior to enrollment that, in the investigator's opinion, may place the participant at risk of side effects from anti-angiogenesis products.
- •History of gastrointestinal bleeding, gastric stress ulcerations, or peptic ulcer disease within the past 3 months prior to enrollment that, in the investigator's opinion, may place the participant at risk of side effects from anti-angiogenesis products.
- •Myocardial infarction or an unstable angina pectoris within 3 months prior to enrollment.
- •Prior major surgery or fracture within 3 weeks prior to enrollment or presence of any non-healing wound (procedures such as catheter placement are not considered to be major).
Arms & Interventions
Apatinib with Nivolumab
Participants will receive an oral dose of apatinib once per day with a fixed dose of nivolumab given intravenously every 2 weeks.
Intervention: Apatinib
Apatinib with Nivolumab
Participants will receive an oral dose of apatinib once per day with a fixed dose of nivolumab given intravenously every 2 weeks.
Intervention: Nivolumab
Outcomes
Primary Outcomes
Number of Participants with Treatment Emergent Adverse Events (TEAEs)
Time Frame: Up to approximately 5 years
Objective Response Rate (ORR): Percentage of Participants who Achieve Confirmed Complete Response (CR) or Partial Response (PR)
Time Frame: Up to approximately 5 years
ORR per the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and/or iRECIST criteria.
Best Overall Response Rate (BOR)
Time Frame: Up to approximately 5 years
BOR is the best response, according to RECIST v1.1 and/or RECIST criteria, recorded over the duration of the study until disease progression, or recurrence.
Time To Response (TTR)
Time Frame: Up to approximately 5 years
TTR is the time lapsed from enrollment until documented response according to RECIST v1.1 and/or iRECIST criteria.
Duration of Response (DoR)
Time Frame: Up to approximately 5 years
DoR is the time from documented tumor response (PR or CR) until disease progression or death from any cause, whichever occurs first.
Disease Control Rate (DCR)
Time Frame: Up to approximately 5 years
DCR is the proportion of participants with radiologically documented stable or decreased tumor burden per RECIST v1.1 and/or iRECIST criteria.
Duration of Disease Control (DDC)
Time Frame: Up to approximately 5 years
DDC is the time from enrollment until disease progression or death from any cause, whichever occurs first. Disease progression will be evaluated by RECIST v1.1 and/or iRECIST criteria.
Secondary Outcomes
- Overall Survival (OS)(Up to approximately 5 years)
- Event Free Survival (EFS)(Up to approximately 5 years)
- Progression Free Survival (PFS)(Up to approximately 5 years)